2024_histology_of_male_reproductive_system.ppt

Learning Objectives for Competency-based Undergraduate Medical Education* Describe the microscopic organization of the testis and correlate with its function. Clinical Histology Thomas Gould,Ph.D. Male Associate Professor Reproductive [email protected]. edu Explain the process of spermatogenesi...

Learning Objectives for Competency-based Undergraduate Medical Education* Describe the microscopic organization of the testis and correlate with its function. Clinical Histology Thomas Gould,Ph.D. Male Associate Professor Reproductive [email protected]. edu Explain the process of spermatogenesis and describe the features and location of each cell type in seminiferous tubules (spermatogonia, primary spermatocytes, secondary spermatocytes, spermatids). Compare features of Sertoli and Leydig cells and explain their role in the testis-blood barrier and in androgen production. Describe the histology of the male genital ducts and correlate with their locations and functions. Compare the histology, location and function of the seminal vesicles, prostate gland and bulbourethral glands. Correlate the histological organization of the penis with the mechanism of erection. Describe the histological structure of the scrotum and define the 4 ways by which it facilitates spermatogenesis. Extend Your Knowledge Base Male Reproductive Anatomy  Seminiferous Tubules; 900*0.5m Spermatogenesis; in testis Sperm sent to rete testis(15-20)  Rete Testis Anastomosing network of tubules Sperm begin to become concentrated Epididymis; (EpiD) 6m Sperm get here thru efferent ductules Resorbs fluid to concentrate sperm Sperm further develop; e.g., motility  Vas deferens (Vd) Enlarges at ampulla Delivers sperm into prostatic urethra  Seminal vesicles (SV) Dumps secretions into prostatic urethra  Prostate gland (PG) Dumps secretions into prostatic urethra  Prostatic, membranous, penile urethra Last connector from testes to exterior  Bulbourethral (Cowper’s) glands Supplies urethra with mucus Genital System – Embryology recap Indifferent gonad – Once PGC arrive, epithelium proliferates and penetrates underlying mesenchyme – Form primitive sex cords in cortex and medulla of ridge – At GW6, sex cords still indistinguishable in M / F Testes cords form in M at GW7 – Extend deep into medulla – PGC form spermatogonia – Joined by Sertoli (coelomic epi) and Leydig (mesenchyme) Genital System – Male Embryology recap Rearrangement of mesonephros – Mesonephric / Wolffian duct (1) used to drain mesonephric nephrons (11) – Now this nephron (2) and proximal meso tubules degenerate – Duct (1) and distal mesonephric tubules connect with testes cords (7) Deep: mesonephric tubules become efferent ductules (5) Paramesonephric duct dies – Connect meso / Wolffian duct (1) to rete testes (6) – PGC form spermatogonia Superficial: testes cords become seminiferous tubules (2) – Connect to rete testes (9) – Pathway exists from seminiferous tubules (st) to Wolffian duct – st solid until puberty Deep: mesonephric duct becomes coiled into epididymis under influence of T – Wolffian duct grows and is transformed into vas deferens under influence of T Spermatogenesis – recap Timing of spermatogenesis – Spermatogonia (Sg) 1.) Divide by mitosis embryonically 2.) Dormant until puberty 3.) Assymmetric mitotic divisions a.) Produce 1 Sg + 1 10 spermatocyte 4.) 10 spermatocyte→ replicate DNA Basal Compartment a.) GnRH→FSH,LH a.) Undergo 2 meiotic divisions b.) Produces 4 haploid spermatids 5.) Spermiogenesis – spermatids differentiate into spermatozoa a.) Acquisition of head (acrosome) b.) Acquisition of midpiece (mitochondria) c.) Acquisition of tail (cytoskeleton) Normal - 50-100 million sperm/cc Infertile - less than 20 million/cc Adlumenal Compartment Spermatogenesis – recap Spatial gradient – Seminiferous tubule of testis 1.) Basal lamina divides: 2.) Sertoli cell tight junctions divide: a.) Basal compartment b.) Adluminal compartment – spermatocytes c.) aka blood-testis barrier Basal Compartment a.) Interstitial compartment – Leydig cells b.) Basal compartment – spermatogonia 3.) Centripetal a.) From basal to adluminal compartment b.) i.e., more immature cells are basal and more differentiated cells are apical or toward the lumen Adlumenal Compartment Spermatogenesis – recap Additional features – Assymmetric division 1.) Type A spermatogonia – mitosis a.) Produces one Type A spermatogonia b.) Produces one Type B spermatogonia, which becomes 10 spermatocyte – Intercellular bridges 1.) Spermatogonia and spermatocytes a.) Unique,0.5 – 3 m-diameter bridges 1.) Large enough to pass organelles! 2.) Gap junction 1-3 nm b.) Synchronize divisions – Sperm gain motility in 2 regions 1.) Epididymis (tail) 2.) Fallopian / uterine tubes - capacitation a.) Makes sperm hyper-motile b.) Removal of cholesterol on sperm head c.) Depolarization Scrotum – recap Position keeps testes 2-3 degrees lower – Dartos muscle / fascia 1.) Contractile state changes surface area of scrotal skin and vascular flow – Cremaster 1.) Raises or lowers testes closer to abdomen – Sweat glands 1.) Secrete water to surface of skin – Countercurrent heat exchange 1.) Pampiniform plexus a.) Venous blood cools warmer arterial blood before it enters testes b.) Arterial blood heats cooler venous blood before its central entry Scrotum – Histology Layers –Tunica vasculosa 1.) Inner vascular layer – not shown – Tunica albuginea 1.) Dense connective tissue 2.) Forms capsule that covers testis 3.) Forms septa: divide testis into lobules – Tunica vaginalis 1.) Serous, covers tunica albuginea 2.) A reflected fold with a.) Inner (visceral) layer b.) Outer (parietal) layer – Cremaster 1.) Skeletal muscle 2.) Surrounded by a.) Internal spermatic fasc – not shown b.) External spermatic fascia – Tunica dartos 1.) Thin sheet of smooth muscle 2.) Intermingled with fibro-elastic tissue 3.) Criss-cross network with vessels running through spaces between the bundles – Skin 1.) Eccrine sweat glands Scrotum – Histology Layers –Tunica vasculosa (V) 1.) Inner vascular layer – Tunica albuginea (T) – Tunica vaginalis – Cremaster 1.) Not shown 2.) Spermatic fascia not shown – Tunica dartos – Skin 1.) Eccrine sweat glands 2.) Sebaceous gland 3.) Hair follicles visceral tunica vaginalis dartos Testis – Histology Layers – Tunica albuginea; covering and septa – Tunica vasculosa / blood vessels – Seminiferous tubules Two functions – Exocrine – spermatogenesis – Endocrine – steroidogenesis (T, E2) Seminiferous tubules – Histology Peritubular connective tissue sheath – Blood vessels, lymphatics, myoepithelial cells Basement membrane Complex, stratified epithelium – Spermatogonia, spermatocytes, spermatids – Sertoli cells Surrounded by interstitium – Leydig cells Seminiferous tubules – Histology ST = seminiferous tubule CT = connective tissue MC = myeloid cell F = fibroblasts Sg spermatogonia Arrowheads = basement membrane PS = primary spermatocyte BC basal compartment AC = adluminal compartment SE seminiferous epithelium Sp = spermatids Ap = spermatozoa pale spermatogonia Sz = n nucleoli L = lumen B spermatogonia B SC= Sertoli cells A arterioles V venules Ad dark spermatogonia SC Sertoli cells SE = seminiferous epithelium Sertoli cells – recap Columnar cells – Span basement membrane to lumen – Form junctional complexes 1.) Tight junctions 2.) Form blood-testis barrier a.) Substances cannot pass into the adluminal compartment b.) Sperm = different antigenicity from somatic cells 1.) Barrier prevents auto-immune response 2.) Also protects against drugs, toxins – Regulate spermatogenesis 1.) FSH receptors – FSH from APG causes Sertoli cells to secrete a # of factors: a.) Androgen binding protein (ABP) 1.) Same protein as SHBG made by liver 2.) Binds T and keeps its levels high b.) Anti-Mullerian hormone (AMH) 1.) Kills off nascent paramesonephric / Mullerian duct 2.) No uterine tube, uterus, and upper vagina in male! c.) Inhibin – neg feedback to hypo-pituitary axis (HPA), esp. FSH d.) Aromatase – E2: negative feedback to HPA resorption of luminal fluid in epididymis 2.) Phagocytose excess spermatid cytoplasm a.) Called residual bodies Interstitial cells of Leydig–recap Large cells found in interstitium along with blood vessels and lymphatics – Secrete testosterone during fetal period 1.) Shuts off at birth, dormant until puberty a.) LH stimulates T production – Testosterone effects – recap 1.) Required for spermatogenesis a.) Requires 70 ng/ml; impaired < 20 ng/ml 2.) Stimulates Leydig cell growth a.) Autocrine, through androgen R (AR) 3.) Stimulates Sertoli cell function a.) Paracrine, through androgen R (AR) 4.) Differentiates male internal genitalia a.) Epididymis, vas deferens, seminal vesicles b.) (PG and urethral glands by DHT) 5.) Feedback inhibition of HPA IC = interstitial cell N = nucleus of interstitial cell ST= seminiferous tubule LV = lymphatic vessels BV = blood vessel St = stroma Hormonal Control of Spermatogenesis – recap GnRH from hypothalamus: – LH and FSH from APG 1.) LH induces Leydig cells to make T 2.) FSH induces Sertoli cells to make factors that regulate spermatogenesis 3.) Feedback regulation by T, E2, inhibin on HPA From Testes to Vas deferens… Rete testes –Anastomosing tubule network 1.) Concentrates sperm Efferent ductules – Ciliated 1.) Moves sperm to epididymis Epididymis – Confers motility – Site of storage Vas deferens – Transports sperm to urethra (EJ duct) Efferent Ductules – Histology Mucosa – Pseudostratified columnar epithelium 1.) Appears as multiple columnar layers but is not a.) Ciliated tall cells (CC) 1.) Cilia move fluid b.) Non-ciliated short cells (NcC) 1.) Microvilli for fluid resorption c.) Sawtoothed or scalloped or stellate appearance Thin layer of CM surrounding – Contractions move sperm to epididymis Epididymis – Histology basal cells Pseudostratified columnar epithelium – Basal cells (stem cells) – Principal cells with stereocilia 1.) Fluid resorption – under E2 2.) Same height; smooth lumen – Efferent ductules often in same section Site where motility is induced Storage site stereocilia – In humans only non-ciliated cells Vas deferens – Histology Mucosa – thrown into longitudinal folds – Pseudostratified columnar epi 1.) Basal cells 2.) Principal cells with sterocilia 3.) Star-shaped lumen – Lamina propria with elastic fibers No submucosa Muscularis externa – Inner longitudinal – Middle circular – Outer longitudinal Adventitia Ends in ejaculatory duct (ED) – Deposits sperm into prostatic urethra – Paired duct, also deposits secretions from SV Function – Sperm transport into urethra – Sperm storage (?) – Dead sperm resorption Seminal vesicles – Histology Mucosa – Pseudostratified columnar epi 1.) Height varies with testosterone levels – Lamina propria with elastic fibers No submucosa Muscularis Externa – IC,OL 1.) Interwoven with connective tissue Adventitia Secretory product – Yellow, viscous fluid – Pale, yellow color of semen due to lipochrome pigment released by seminal vesicles – Rich in fructose and prostaglandins – Accounts for ~70% of ejaculate Prostate Gland – recap Structure – Surrounds urethra as it exits bladder – ~30 tubulo-alveolar glands in fibromuscular stroma Prostate Gland – recap Structure – 3 concentric layers around prostatic urethra 1.) Mucosal – peri-urethral zone 2.) Submucosal – transitional zone 3.) Main prostatic glands – peripheral zone – Secretory product 1.) Whitish, thin, fluid-rich, pH 6.5 2.) Citric acid, for energy 3.) Prostatic acid phosphatase 4.) Fibrinolysin (liquefies semen bolus once in female tract) 5.) PSA – also liquefies semen bolus 6.) ~30% of ejaculate 7.) Deposited into prostatic urethra through prostatic duct Prostate Gland – recap Structure – 3 concentric layers around prostatic urethra 1.) Mucosal – peri-urethral zone 2.) Submucosal – transitional zone 3.) Main prostatic glands – peripheral zone – Clinical correlation 1.) Benign prostatic hyperplasia a.) Mucosal and submucosal glands b.) 40% of men > 50; 95% of men >80 c.) Inability to begin or stop urine flow, nocturia, sensory urgency d.) Prostate-specific Antigen (PSA) levels 2.) Prostatic carcinoma a.) Main prostatic glands b.) Digital rectal exam – feel for induration (firmness) or masses (nodules) c.) Prostate-specific Antigen (PSA) levels Prostate Gland – Histology Structure – 3 concentric layers around prostatic urethra 1.) Mucosal – peri-urethral zone 2.) Submucosal – transitional zone 3.) Main prostatic glands – peripheral zone Anterior fibromuscular stroma Prostate Gland – Histology Tissue Layers – Mucosa – glandular (tubulo-alveolar/-acinar) 1.) Stratified columnar epithelium a.) Outer basal cells – cuboidal b.) Inner luminal cells – columnar 2.) Thin lamina propria 3.) Corpora amylacea – age-dependent calcifications – No submucosa – Muscularis externa 1.) Fibromuscular stroma, rather than muscle layers – Fibro-elastic capsule Bulbourethral glands (Cowper’s) – Histology Located in uro-genital diaphragm – Small piece of skeletal muscle through which membranous urethra passes – Secretions emptied into proximal portion of penile / spongy urethra 1.) Alkaline fluid rich in mucus a.) Lubrication during intercourse, released before ejaculation b.) Balances acidic pH of urine in male urethra, as well as of female tract Bulbourethral glands (Cowper’s) – Histology Tissue structure – Mucinous glands with ducts – also tubulo-alveolar (1) 1.) Alveoli lined by cuboidal epi 2.) Collecting ducts lined by cuboidal or columnar epi 3.) Large intraglandular ducts lined by pseudostratified columnar epi – Lodged within bulbocavernosus (2; skeletal muscle) 1 Penis – Histology Tissue structure – 3 cylindrical bundles of erectile tissue 1.) Trabeculated, spongy appearance 2.) Surrounded by connective tissue (CT) sheath a.) 2 Corpora cavernosa – dorsal; thick tunica albuginea (TA) CT b.) 1 Corpus spongiosum – ventral, thin tunica albuginea CT, surrounds penile urethra (U) 3.) CT surrounded by buck fascia, dartos fascia, and dry, hairless skin TA TA U Penis – Histology Tissue structure – 3 cylindrical bundles of erectile tissue 3.) Supplied by helicine arteries a.) From deep artery of penis, from internal pudendal artery b.) Coiled in an intimal cushion – little blood flow; sympathetic basal tone c.) Parasympathetic – dilation via NO, blood flows in – coils prevent backflow, act as valves Urethra – Histology Tissue layers of 4 regions of urethra – Pre-prostatic region – bladder to PG – ~1 cm 1.) Mucosal epi – transitional epithelium, aka urothelium a.) Can change from cuboidal to squamous with stretch b.) Columnar near basement membrane; rounded toward lumen 2.) Mucosal lamina propria 3.) Muscularis externa (bladder) a.) Inner longitudinal, middle circular, outer longitudinal – Prostatic region – within PG, ~3-4 cm 1.) Urothelium + lamina propria 2.) Surrounded by glandular, fibromuscular stroma of PG – Membranous region – between PG and penis, ~1 cm 1.) Pseudostratified columnar epithelium + lamina propria a.) Appears as multiple columnar layers but is not 2.) Skeletal muscle at level of external urethral sphincter 3.) Bulbo-urethral glands may be present – Penile region – within penis, ~15 cm 1.) Pseudostratified columnar epithelium (E) + lamina propria a.) At external meatus, stratified squamous epi 2.) Corpora spongiosum surrounds urethra a.) Trabecular smooth muscle 3.) Peri-urethral glands, aka glands of Littré, may be present a.) Secrete mucus into lumen like Cowper’s